Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age

PURPOSE: To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age. METHODS AND MATERIALS: Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia. RESULTS: The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by up to a factor of approximately 2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1% (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk. CONCLUSION: The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role.     

Monte Carlo study shows no significant difference in second cancer risk between 6- and 18-MV intensity-modulated radiation therapy

Purpose

To evaluate the photon and neutron out-of-field dose equivalents from 6- and 18-MV intensity-modulated radiation therapy (IMRT) and to investigate the impact of the differences on the associated risk of induced second malignancy using a Monte Carlo model.

Methods and materials

A Monte Carlo model created with MCNPX was used to calculate the out-of-field photon dose and neutron dose equivalent from simulated IMRT of the prostate conducted at beam energies of 6 and 18 MV. The out-of-field dose equivalent was calculated at the locations of sensitive organs in an anthropomorphic phantom. Based on these doses, the risk of secondary malignancy was calculated based on organ-, gender-, and age-specific risk coefficients for a 50-year-old man.

Results

The Monte Carlo model predicted much lower neutron dose equivalents than had been determined previously. Further analysis illuminated the large uncertainties in the neutron dose equivalent and demonstrated the need for better determination of this value, which plays a large role in estimating the risk of secondary malignancies. The Monte Carlo calculations found that the differences in the risk of secondary malignancies conferred by high-energy IMRT versus low-energy IMRT are minimal and insignificant, contrary to prior findings.

Conclusions

The risk of secondary malignancy associated with high-energy radiation therapy may not be as large as previously reported, and likely should not deter the use of high-energy beams. However, the large uncertainties in neutron dose equivalents at specific locations within the patient warrant further study so that the risk of secondary cancers can be estimated with greater accuracy.     

Second cancer risk after 3D-CRT,IMRT and VMAT for breast cancer

Purpose

Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED).

Materials and methods

Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk.

Results

Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively.

Conclusion

Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively.     

Early biomarkers related to secondary primary cancer risk in radiotherapy treated prostate cancer patients: IMRT versus IMAT

Purpose

To investigate whether rotational techniques (Volumetric Modulated Arc Therapy – VMAT) are associated with a higher risk for secondary primary malignancies compared to step-and-shoot Intensity Modulated Radiation Therapy (ss-IMRT). To this end, radiation therapy (RT) induced DNA double-strand-breaks and the resulting chromosomal damage were assessed in peripheral blood T-lymphocytes of prostate cancer (PCa) patients applying γH2AX foci and G₀ micronucleus (MN) assays.

Methods and materials

The study comprised 33 PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced γH2AX foci and MN. The equivalent total body dose (D_ETB) was calculated based on treatment planning data.

Results

A linear dose response was obtained for γH2AX foci yields versus D_ETB while MN showed a linear-quadratic dose response. Patients treated with large volume (LV) VMAT show a significantly higher level of induced γH2AX foci and MN compared to IMRT and small volume (SV) VMAT (p < 0.01). Assuming a linear-quadratic relationship, a satisfactory correlation was found between both endpoints (R² 0.86).

Conclusions

Biomarker responses were governed by dose and irradiated volume of normal tissues. No significant differences between IMRT and rotational therapy inherent to the technique itself were observed.     

Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer

Background and purpose

Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN.

Materials and methods

Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n = 40 plans) and dose-volume histograms were generated.

Results

The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p = 0.020) and mean doses to the contralateral parotid gland (p = 0.049) and larynx (p = 0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lowered the maximum doses to the spinal cord (p < 0.002 for both) and brainstem (p < 0.002 for both) and mean doses to the larynx (p < 0.002 for both) and ipsilateral (p = 0.004 IMRT, p = 0.050 adaptive) and contralateral (p < 0.002 IMRT, p = 0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT.

Conclusions

Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.     

儿童颅咽管瘤质子和光子治疗的剂量学比较

目的：对3例儿童颅咽管瘤进行剂量学比较，以探讨质子在儿童颅咽管瘤放疗中的潜在优越性。方法：靶区肿瘤照射剂量为55Cy。每例患者分别作单纯光子、光子和质子混合射线以及单纯质子的治疗计划，治疗方法均为三维适形治疗；应用适形指数以量化地比较3种治疗计划对靶区的剂量覆盖和正常组织的照射容积和剂量。结果：3种治疗计划均达到满意的靶区剂量覆盖，92％～100％的PTV在处方剂量95％的范围内。质子治疗的运用使得正常脑组织、脑干、大脑颞叶和内耳的剂量显著下降。当肿瘤与视交叉有少许间隙时，质子治疗可以降低视交叉的平均剂量和最低剂量。单纯质子体现出较混合射线更强的优越性。单纯光子、混合射线和单纯质子的适形指数分别为O．631、O．784和O．848，即质子治疗提供的高剂量区曲线分布更符合PTV的形状。结论：在保证靶区剂量的基础上，质子的应用普遍减少了颅内正常组织的照射，并在部分患者中提供了剂量提升的可能性。     

螺旋断层放疗与常规调强放疗在乳腺癌保乳术后同步推量中的剂量学比较

目的 比较乳腺癌保乳术后同步推量放疗中应用常规调强放疗（IMRT）及螺旋断层放疗（HT）剂量分布的差异,为HT在乳腺癌保乳术后的临床应用提供依据。方法 随机选择10例乳腺癌保乳术后患者,统一勾画计划靶区（PTV）与原发灶靶区（PGTV）并导入HT计划系统及瓦里安Eclipse计划系统,分别设计IMRT和HT计划,处方剂量均为PTV 50Gy／25f、PGTV 60Gy／25f,通过比较靶区剂量适形度、均匀性以及心肺受照剂量来评估IMRT与HT的优劣。结果 HT计划中靶区剂量的均匀性、适形度明显优于IMRT（P＜0.05）,患侧肺V5、V10、V20、V30及肺平均剂量均明显低于IMRT（P＜0.05）,但健侧肺V5增加;心脏剂量明显降低（P＜0.05）。结论 对于乳腺癌保乳术后同步推量放疗,HT与IMRT计划都可以满足临床剂量的要求,但HT计划在剂量学方面相对于IMRT计划具有优势,可以显著降低对正常器官的毒副作用。     

Effect of anatomic motion on proton therapy dose distributions in prostate cancer treatment

PURPOSE: To determine the dosimetric impact of interfraction anatomic movements in prostate cancer patients receiving proton therapy. METHODS AND MATERIALS: For each of the 10 patients studied, 8 computed tomography (CT) scans were selected from sets of daily setup CT images that were acquired from a cohort of prostate cancer patients. The images were acquired in the treatment room using the CT-on-rails system. First, standard proton therapy and intensity-modulated radiation therapy (IMRT) plans were designed for each patient using standard modality-specific methods. The images, the proton plan, and the IMRT plan were then aligned to the eight CT images based on skin marks. The doses were recalculated on these eight CT images using beam from the standard plans. Second, the plans were redesigned and evaluated assuming a smaller clinical target volume to planning target volume margin (3 mm). The images and the corresponding plans were then realigned based on the center of volume of the prostate. Dose distributions were evaluated using isodose displays, dose-volume histograms, and target coverage. RESULTS: For the skin-marker alignment method, 4 of the 10 IMRT plans were deficient, whereas 3 of 10 proton plans were compromised. For the alignment method based on the center of volume of the prostate, only the proton plan for 1 patient was deficient, whereas 3 of the 10 IMRT plans were suboptimal. CONCLUSION: A comparison of passively scattered proton therapy and highly conformal IMRT plans for prostate cancer revealed that the dosimetric impact of interfractional anatomic motions was similar for both modalities.     

宫颈癌VMAT与静态IMRT所致全身当量剂量比较

目的 比较VMAT和静态IMRT技术在宫颈癌放疗中所致患者全身当量剂量。方法选取2014年间收治的9例宫颈癌放疗患者, 针对每例患者设计出VMAT和IMRT计划。在进行VMAT和IMRT治疗中,使用热释光剂量计(TLDs)测量每例患者在剑突和眉间位置上的当量剂量Hp(10),并基于剑突位置上测量的当量剂量估算出患者全身当量剂量。配对t检验二者差异。结果采用VMAT技术在每例患者剑突和眉间位置上测量的当量剂量均低于IMRT技术。当给予患者50 Gy处方剂量,选取患者剑突位置的平均当量剂量作为代表患者全身当量剂量时,WMAT和IMRT放疗技术所致患者的全身当量剂量分别为364 mSv和538 mSv。结论 VMAT技术比IMRT技术可导致患者更低的全身当量剂量, 可降低辐射诱发癌症发生的危险度。     

Disruption to radiation therapy sessions due to anxiety among patients receiving radiation therapy to the head and neck area can be predicted using patient self-report measures

Objective: This analysis sought to determine whether patient self‐report measures were associated with disruption to radiation therapy sessions due to anxiety among cancer patients undergoing radiation therapy to the head and neck region. Method: A cohort of patients undergoing radiation therapy to the head and neck region at a major regional radiation oncology treatment centre (ROTC) in Australia completed self‐report measures of anxiety, history of panic and fears relevant to use of an immobilising mask. The treating Radiation Therapist (RT) rated the level of session disruption due to patient anxiety during the Computerised Tomography/Simulation (CT/Sim) (baseline) session and first treatment session. Results: Complete data were obtained for 90 patients. RTs rated 11 and 24% of patients as having some level of session disruption session due to anxiety at baseline and Treatment 1, respectively. Five factors were significantly associated with session disruption at baseline in bivariate analyses: currently taking psycho‐active medication (p=0.008); fear of enclosed spaces (p=0.006); fear of face being covered up (p=0.006); fear of movement restriction (p=0.041) and ever had an anxiety attack (p=0.034). Sensitivity ranged from 0.57 to 0.75 and specificity ranged from 0.68 to 0.90. Only session disruption at baseline predicted disruption at Treatment 1 (p<0.01). Conclusions: This study offers some preliminary insights into the prevalence of patient anxiety severe enough to cause session disruption and patient self‐report measures which might be used to flag patients for prophylactic treatment. Further development and replication in a larger sample is warranted before introduction of these measures into routine practice. Copyright © 2010 John Wiley & Sons, Ltd.     

调强放疗联合NP方案同步与序贯治疗中晚期非小细胞肺癌的疗效观察

Objective： To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer （NSCLC） useing IMRT combined with NP regimen chemotherapy. Methods： Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine＋cispatin （NP） was used in chemotherapy. Results： （1） The overall response （CR＋PR） rate was 75% in concurrent group and 45% in sequential group （P〈0.05）; （2） The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively （P〈0.05）; （3） One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; （4） The toxic effects can be tolerable by all of patients. Conclusion： The concurrent chemo-radiotherapy has better overall response, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.     

调强放疗联合NP方案同步与序贯治疗中晚期非小细胞肺癌的疗效观察

目的:比较调强放疗联合NP方案同步与序贯治疗中晚期非小细胞肺癌的临床疗效。方法:选择不能手术的中晚期非小细胞肺癌(NSCLC)患者80例,随机分成同步组和序贯组各40例。放疗采用调强放疗,化疗采用NP方案(盖诺 顺铂)。结果:(1)治疗总有效率比较(CR PR):同步组75·0%,序贯组45·0%,两组比较差异有显著性(P<0·05);(2)两组的总治疗时间比较:同步组平均84天,序贯组平均为140天,两组比较差异有显著性(P<0·05);(3)生存率(Kaplan-Meier法)比较:同步组1年生存率为72·4%,序贯组为52·3%,两组比较差异有显著性(P<0·05);(4)两组病人均能耐受治疗中的不良反应。结论:同步组的近期疗效明显优于序贯组,能提高患者的1年生存率,且能缩短住院周期,减轻患者的经济负担,但远期生存率的比较有待进一步观察。     

Using decision analysis to determine the cost-effectiveness of intensity-modulated radiation therapy in the treatment of intermediate risk prostate cancer

BACKGROUND: The specific aim of this study is to evaluate the cost-effectiveness of intensity-modulated radiation therapy (IMRT) compared with three-dimensional conformal radiation therapy (3D-CRT) in the treatment of a 70-year-old with intermediate-risk prostate cancer. METHODS: A Markov model was designed with the following states; posttreatment, hormone therapy, chemotherapy, and death. Transition probabilities from one state to another were calculated from rates derived from the literature for IMRT and 3D-CRT. Utility values for each health state were obtained from preliminary studies of preferences conducted at Fox Chase Cancer Center. The analysis took a payer's perspective. Expected mean costs, cost-effectiveness scatterplots, and cost acceptability curves were calculated with commercially available software. RESULTS: The expected mean cost of patients undergoing IMRT was $47,931 with a survival of 6.27 quality-adjusted life years (QALYs). The expected mean cost of patients having 3D-CRT was $21,865 with a survival of 5.62 QALYs. The incremental cost-effectiveness comparing IMRT with CRT was $40,101/QALYs. Cost-effectiveness acceptability curve analysis revealed a 55.1% probability of IMRT being cost-effective at a $50,000/QALY willingness to pay. CONCLUSION: Intensity-modulated radiation therapy was found to be cost-effective, however, at the upper limits of acceptability. The results, however, are dependent on the assumptions of improved biochemical disease-free survival with fewer patients undergoing subsequent salvage therapy and improved quality of life after the treatment. In the absence of prospective randomized trials, decision analysis can help inform physicians and health policy experts on the cost-effectiveness of emerging technologies.     

Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer

Introduction

Volumetric modulated arc therapy (VMAT), a complex treatment strategy for intensity-modulated radiation therapy, may increase treatment efficiency and has recently been established clinically. This analysis compares VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT) delivery techniques.

Methods

Based on CT datasets of 9 patients treated for prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT were compared with regard to plan quality and treatment efficiency. Two VMAT approaches (one rotation (VMAT1x) and one rotation plus a second 200° rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was assessed by calculating homogeneity and conformity index (HI and CI), dose to normal tissue (non-target) and D_95% (dose encompassing 95% of the target volume). For plan efficiency evaluation, treatment time and number of monitor units (MU) were considered.

Results

For MIMiC/IMRT_MLC/VMAT2x/VMAT1x/3D-CRT, mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99 Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85 Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non-target normal tissue receiving ?70% of prescribed dose (53 Gy) were 337 ml/284 ml/482 ml/505 ml/414 ml, for ? 50% (38 Gy) 869 ml/933 ml/1155 ml/1231 ml/1993 ml and for ? 30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml. D_95% was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was 12 min/6 min/3.7 min/1.8 min/2.5 min.

Conclusion

All approaches yield treatment plans of improved quality when compared to 3D-conformal treatments, with serial tomotherapy providing best OAR sparing and VMAT being the most efficient treatment option in our comparison. Plans which were calculated with 3D-CRT provided good target coverage but resulted in higher dose to the rectum.     

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ⩾70 patients, and ⩾5 year median follow up. Twenty-six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45–90%, 40–60%, and 20–50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high-risk patients have generally been >85%, 69–97%, 63–80%, respectively) and BT + EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82–97%, 1–14%, 0–8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through Grade 3–4 toxicities were rare (<5%) among all modalities. There was limited evidence available to compare proton therapy to other modalities. The treatment decision for a man is usually based on his risk group, ability to tolerate the procedure, convenience for the patient, and the anticipated impact on quality of life. To further personalize therapy, future trials should report (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education status; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics.